Healthy Volunteers, Rheumatoid Arthritis
Conditions
Keywords
Phase 1, healthy volunteers, pharmacokinetics, Rheumatoid arthritis, RA, Fostamatinib, Digoxin, drug-drug interaction, Scientific terminology: Rheumatoid arthritis, Fostamatinib, Digoxin, drug-drug interaction, Laymen terminology: Rheumatoid arthritis, Amount of Digoxin in blood
Brief summary
The purpose of this study is to investigate the drug interaction between fostamatinib and digoxin by comparing the safety, tolerability and plasma concentration of digoxin when administered alone and with fostamatinib in healthy subjects.
Interventions
DRUGDigoxin
oral tablets, 0.25mg bd on Day 1 and 0.25 Once daily from Day 2 to 15
DRUGFostamatinib
oral tablets, 100mg (2 X 50mg) bd from Day 9 - 15
Sponsors
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Provision of informed consent prior to any study specific procedures * Male or female subjects aged 18 to 45 years (inclusive) * Minimum weight of 50 kg and body mass index (BMI) between 18 and 30 kg/m2 (inclusive) * Female subjects must have a negative pregnancy test at screening and on Day -1,must not be lactating, and must be of non-childbearing potential
Exclusion criteria
* History or presence of gastrointestinal, hepatic, or renal disease or any other condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs (except for cholecystectomy) * Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of the first administration of the investigational product * Subjects who smoke more than 5 cigarettes or the equivalent in tobacco per day * Absolute neutrophil count of \<2500/mm3 or 2.5 x 109/L * Previous treatment with fostamatinib or digoxin in the present study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To investigate whether the plasma concentration-time profiles and resulting PK parameters of digoxin are altered during steady-state fostamatinib administration. Digoxin AUCss and Cmaxss will be measured | Day 8 and Day 15 |
Secondary
| Measure | Time frame |
|---|---|
| To examine the safety + tolerability of fostamatinib in combination with digoxin. Assessments: Adverse events, lab assessments, vital signs, phys exam,12-lead ECG. Absolute values and change in baseline for any of these parameters will be reported | From screening, Day 1 - Day 17, through to Follow up visit |
| To examine the steady-state PK of R406 during co-administration of fostamatinib with digoxin at steady-state. R406 AUCss, tmaxss and Cmaxss will be measured | Day 15 |
| To examine the urinary steady-state PK of digoxin in healthy subjects when administered alone and in combination with fostamatinib at steady-state. Digoxin Ae(0-t), Fe, and CLr will be measured | Day 8 and Day 15 |
Countries
United Kingdom
Outcome results
None listed